Viral infections in the normal host are usually self-limited as the innate and acquired immune systems mount successful antiviral responses. However, in some instances, apparently immunocompetent persons manifest infections with viruses that would otherwise be observed only in severely immunocompromised hosts. For example, cases of herpes simplex virus (HSV) encephalitis, esophagitis orgastritis, cytomegalovirus (CMV) colitis, adenovirus hepatitis or pneumonitis, recurrent or persistent skin infections caused by HSV or varicella zoster virus (VZV), severe warts caused by human papillomavirus (HPV), recurrent respiratory papillomatosis caused by HPV, severe influenza or respiratory syncytial virus pneumonia, and progressive multifocal leukoencephalopathy (PML) due to JC polyomavirus have been described in apparently immunocompetent patients. While a variety of case reports have described severe viral infections in immunocompetent hosts, the pathogenesis of the vast majority of these cases is not understood, and therapy can be unsuccessful.